Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
J Immunol Methods. 2018 Sep;460:10-16. doi: 10.1016/j.jim.2018.06.002. Epub 2018 Jun 15.
Ebolaviruses are highly virulent pathogens that cause Ebola viral disease (EVD). Data from non-human primate (NHP) models and from human survivors of EVD suggest that anti-Ebola antibodies play an integral role in protection. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potential mechanism through which anti-Ebola antibodies may mediate protection. We developed a robust Ebola-specific ADCC assay for use in ongoing trials of Ebola vaccines. Stable cell lines for inducible Zaire ebolavirus glycoprotein (EBOV GP) expression were developed to provide a uniform source of target cells in the assay, and were combined with an existing human natural killer (NK) cell line as the effector cell. When applied to commercially available anti-EBOV GP monoclonal antibodies, the assay clearly differentiated antibody with high ADCC activity from those with low or no ADCC activity. Anti-EBOV ADCC activity was also detected in plasma samples from rhesus macaques immunized with a candidate Ebola vaccine. The Ebola ADCC assay reported here will be a useful tool in studying the functionality of anti-EBOV GP antibodies elicited by Ebola vaccines in ongoing and future clinical trials.
埃博拉病毒是一种高致病性病原体，可引起埃博拉病毒病（EVD）。来自非人类灵长类动物（NHP）模型和 EVD 幸存者的人类数据表明，抗埃博拉病毒抗体在保护中起着重要作用。抗体依赖性细胞介导的细胞毒性（ADCC）是抗埃博拉病毒抗体可能介导保护的一种潜在机制。我们开发了一种强大的埃博拉特异性 ADCC 测定法，用于正在进行的埃博拉疫苗试验。稳定的诱导性扎伊尔埃博拉病毒糖蛋白（EBOV GP）表达细胞系用于在测定中提供均匀的靶细胞来源，并与现有的人类自然杀伤（NK）细胞系作为效应细胞结合。当应用于市售的抗 EBOV GP 单克隆抗体时，该测定法清楚地区分了具有高 ADCC 活性的抗体与具有低 ADCC 活性或无 ADCC 活性的抗体。用候选埃博拉疫苗免疫的恒河猴的血浆样本中也检测到抗 EBOV ADCC 活性。本文报道的埃博拉 ADCC 测定法将成为研究正在进行和未来临床试验中埃博拉疫苗引起的抗 EBOV GP 抗体功能的有用工具。
